Hypersensitivity reactions generally known as allergies are called abnormal immune responses against antigens. These reactions are classified into four main types according to the Gell & Coombs classification: type I hypersensitivity reaction mediated by IgE, type II hypersensitivity reaction mediated by antibodies, type III hypersensitivity reaction mediated by immune complexes, and type IV hypersensitivity reaction mediated by interactions between antigen presenting cells and T cells. Allergic diseases commonly found in the surroundings are mostly caused by type I hypersensitivity reaction, and include allergic rhinitis, asthma, allergic dermatitis, and the like. There are foods, such as nuts and eggs, pollen, dust mites, and some drugs which are well known allergens (antigens). These allergens are combined with IgE, attached to α-subunits of FIεRI, which is a IgE receptor of mast cells, and forms complexes together with β and γ-subunits, thereby enabling signaling of the receptors. Through this procedure, the degranulation of mast cells is induced to activate the secretion of histamine, beta-hexosaminidase, prostaglandin, leukotriene, interleukin (IL)-4, IL-5, IL-6, and TNF-α, which are factors that causes itching or inflammation responses. The actions of these factors may be aggravating factors of allergic reactions by activating IgE production of B cells. It has been known that high serum IgE levels are actually observed in allergic patients, and thus the inflow of allergens easily causes hypersensitivity reactions (Allergy Asthma Immunol Res., 5(3): 170-174(2013)).
Diseases are classified according to the area in which type I hypersensitivity reaction is observed. The hypersensitivity reaction results in allergic rhinitis in the nasal mucosa, asthma in the airway mucosa or bronchial tubes, and atopic dermatitis in the skin.
The atopic dermatitis prevalence rate in people over 1 year old people was 6.1% according to the National Health and Nutrition Examination Survey results (National Health and Nutrition Examination Survey, the Ministry of Health and Welfare) reported in 2010, and the atopic dermatitis prevalence rate of 13-18 year old adolescents was 23.1% in the 2011 Youth Health Behavior Online Survey (Youth health behavior online survey, the Ministry of Health and Welfare). Lesions begin due to general allergens or IgE stimulation, and patients scratch the affected parts because of itching caused by the stimulation of histamine secreted from degranulation of mast cells, resulting in, secondarily, the inflow of Staphylococcus aureus, S. epidermidis, and the like, which are skin flora. It is known that the inflow of such foreign antigens may cause additional inflammation responses in the affected parts or worsen diseases (Allergy Asthma Proc., May-June; 33(2012)).
Therapeutic agents for atopic dermatitis include steroids showing anti-inflammatory actions through immunosuppressive effects, antihistamines blocking the release of histamine from mast cells, antibiotics, and the like. However, the steroid use for a long period of time causes side effects, such as hair growing, skin thinning, and bacterial infection, and the steroid withdrawal causes rapid aggravation of symptoms. It has been reported that the antihistamine use for a long period of time causes side effects, such as insomnia, anxiety, and loss of appetite. The antibiotic use for a long period of time also causes side effects, such as antibiotic resistance. Therefore, the development of more effective therapeutic agents capable of minimizing side effects is required.
In vivo proteins can minimize side effects due to high biocompatibility thereof. However, proteins per se have too low stability and high production costs for the use as therapeutic agents. Peptide preparations that use particular effective regions of the in vivo proteins have the same efficacies and can solve problems in association with stability and production costs. Therefore, the present researchers conducted research that utilizes anti-allergic effects of peptides derived from in vivo proteins, capable of suppressing the activation of mast cells.
Semaphorin 3A is one of semaphorin proteins that have a common cysteine-rich domain called a Sema domain. Semaphorin protein was first known as a repulsive axon guidance factor in the nervous system development process. Class 3 semaphorins are secreted proteins, include six kinds ranging from Sema3A to Sema3F, and deliver signals by forming receptor complexes together with Plexin A receptor and Neurophilin receptor. As known in the early stages, semaphorin 3A guides the contraction of nerve growth factor (NGF)-sensitive neurons or is expressed from activated T cells and dendritic cells, thereby regulating T cell growth or cytokine secretion.
Throughout this application, various patents and publications are referenced and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by references into this application in order to more fully describe this invention and the state of the art to which this invention pertains.